tbuckley/cabot-search huggingface dataset:
Brain metastases (mets) in lung cancer patients (pts): Analysis of the Detroit Surveillance, Epidemiology and End Results (SEER) data.
Authors: S. M. Gadgeel, R. Goveas, F. Vigneau, W. Quarshie, M. Islam, A. Schwartz, A. J. Wozniak, M. Cote
Journal: Journal of Clinical Oncology (2010)

7635 Background: Brain mets in lung cancer pts are associated with morbidity and can limit therapeutic options. We conducted an analysis of the Detroit SEER data to describe the occurrence of brain mets in non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC) pts, the demographics, the temporal trends in brain mets, the risk of brain mets in pts with non-metastatic lung cancer at diagnosis and the survival of pts with brain mets. Methods: Caucasian (C) or African-American (AA) lung cancer pts diagnosed between 1973-2007 in the Detroit SEER registry were included. Median survival and 95% confidence intervals (CI) were generated by histology and brain mets status. Cox Proportional Hazards models were generated by histology to compare survival between those with and without brain mets. Results: 75,564 pts were identified; 62,860 (83%) had NSCLC. The proportion of NSCLC pts and SCLC pts with brain mets were 16.4% and 25.1%, respectively. Brain mets occurred significantly more in females with NSCLC (17.7% vs. 15.7%) but not among SCLC pts. Brain mets occurred significantly more in AA pts (18.9% v. 15.6%- NSCLC; 27.6% v. 24.5%- SCLC; p < 0.0001) and pts ≤ 60 yrs (24.5% vs. 13%- NSCLC, 31.4% vs. 22.4%-SCLC, p < 0.0001). The proportion of brain mets for NSCLC and SCLC pts in 1973-84 was 16% and 20.5%, and in 1997-2007 was 16.1% and 24.8%, respectively. The hazard ratio for death among metastatic NSCLC pts with brain mets was significantly greater at 1.13 than in pts without brain mets (1.1-1.16) but for metastatic SCLC it was 0.87 (0.83- 0.92). Among pts with nonmetastatic lung cancer at diagnosis, 9% of NSCLC and 19% of SCLC pts developed brain mets. In these pts, brain mets occurred significantly more among females and patients ≤ 60 yrs. The hazard ratio for death among non-metastatic NSCLC pts who developed brain mets was 1.44 (1.38-1.51) and among SCLC pts was 1.05 (0.96-1.14). Conclusions: The proportion of NSCLC and SCLC pts with brain mets is 16.4 and 25.1%. Brain mets occurred significantly more in females with NSCLC, AA and younger pts. The hazard ratio for death among NSCLC pts with brain mets is significantly greater than in patients without brain mets but not so in SCLC pts. No significant financial relationships to disclose.
Abstract 12195: Right Vagus Nerve Stimulation Improves Left Ventricular Function in Heart Failure: Results of a Cross-Over Study in Dogs with Experimental Heart Failure
Authors: Hani N Sabbah, Jason J Hamann, Mengjun Wang, Itamar Ilsar, Ramesh C Gupta, Sharad Rastogi, Stephen B Ruble
Journal: Circulation (2010)
The natural history of gallstones: The GREPCO experience
Authors: Adolfo Francesco Attili, Adriano de Santis, Rita Capri, Anna Maria Repice, Silvana Maselli, Grepco Group
Journal: Hepatology (1995)

During the cross-sectional studies (February 1981 to July 1984) performed by the Group for Epidemiology and Prevention of Cholelithiasis (GREPCO) in Rome, Italy, 161 subjects were identified as having gallstones. Ten subjects did not participate in the prospective follow-up. At entry, 33 of the 151 remaining subjects were symptomatic, and 118 were asymptomatic. Data on incidence of biliary colics, complications, cholecystectomy, and death were collected at least every 2 years. In the initially asymptomatic group, the cumulative probability (% ± SE) of developing biliary colic was 11.9 ± 3.0 at 2 years, 16.5 ± 3.5 at 4 years, and 25.8 ± 4.6 at 10 years. None of the variables considered as possible modifiers of the natural history were found to be associated with an increased risk of developing biliary colic. The cumulative probability (% ± SE) of developing complications after 10 years was 3.0 ± 1.8 in the initially asymptomatic group and 6.5 ± 4.4 in the symptomatic group ( P = NS). Incidence of cholecystectomy was higher in the initially symptomatic than in the asymptomatic group (log-rank test = 2.27; P = .02). Fifteen (53.6%) of the 28 operated in the initially asymptomatic group were submitted to cholecystectomy, although specific symptoms did not occur. Twelve (10.2%) and 2 (6.1%) of the initially asymptomatic and symptomatic subjects died during the follow-up. One patient in the former group died at age 64 of a histologically proven adenocarcinoma of the gallbladder. In conclusion, this study demonstrates that the natural history of gallstones is less benign than is generally considered.
Analgesic and potentiated photothermal therapy with ropivacaine-loaded hydrogels
Authors: Jiqian Zhang, Shasha Zhu, Mingxu Zhao, Mengni Zhou, Xiaoling Zhu, Xin Qing, Zhilai Yang, Pengfei Wei, Guoying Zhang, Weiling He, Yongqiang Yu, Xuesheng Liu
Journal: Theranostics (2023)

Rationale: Tumor ablation can cause severe pain to patients, but there is no satisfactory means of analgesia available.In addition, recurrence of residual tumors due to incomplete ablation threatens patient safety.Photothermal therapy (PTT), a promising approach for tumor ablation, also faces the aforementioned problems.Therefore, developing novel photothermal agents that can efficiently relieve PTT-associated pain and potentiate the PTT efficacy are urgently needed.Methods: The Pluronic F127 hydrogel doped with indocyanine green (ICG) was served as photothermal agent for PTT.Mouse model that inoculation of tumor near the sciatic nerve was constructed to assess the PTT-evoked pain.Subcutaneous and sciatic nerve vicinal tumor-bearing mice were used to test the efficacy of PTT.Results: PTT-evoked pain depends on an increase in tumor temperature and is accompanied by the activation of TRPV1.A simple introduction of local anesthetic (LA) ropivacaine into ICG-loaded hydrogels relieves PTT-induced pain and exerts long-lasting analgesia compared with opioid analgesia.More interestingly, ropivacaine upregulates major histocompatibility complex class I (MHC-I) in tumor cells by impairing autophagy.Therefore, a hydrogel co-doped with ropivacaine, TLR7 agonist imiquimod and ICG was rationally designed.In the hydrogel system, imiquimod primes tumor-specific CD8 + T cells through promoting DCs maturation, and ropivacaine facilitates tumor cells recognition by primed CD8 + T cells through upregulating MHC-I.Consequently, the hydrogel maximumly increases CD8 + T cells infiltration into tumor and potentiates PTT efficacy.Conclusion: This study for the first time provides an LA-dopped photothermal agents for painless PTT and innovatively proposes that a LA can be used as an immunomodulator to potentiate the PTT efficacy.
Therapeutic effect of ultra-long-lasting human C-peptide delivery against hyperglycemia-induced neovascularization in diabetic retinopathy
Authors: Chan-Hee Moon, Ah-Jun Lee, Hye-Yoon Jeon, Eun-Bin Kim, Kwon-Soo Ha
Journal: Theranostics (2023)

Rationale: Neovascularization is a hallmark of the late stages of diabetic retinopathy (DR) leading to blindness. The current anti-DR drugs have clinical disadvantages including short circulation half-lives and the need for frequent intraocular administration. New therapies with long-lasting drug release and minimal side effects are therefore needed. We explored a novel function and mechanism of a proinsulin C-peptide molecule with ultra-long-lasting delivery characteristics for the prevention of retinal neovascularization in proliferative diabetic retinopathy (PDR). Methods: We developed a strategy for ultra-long intraocular delivery of human C-peptide using an intravitreal depot of K9-C-peptide, a human C-peptide conjugated to a thermosensitive biopolymer, and investigated its inhibitory effect on hyperglycemia-induced retinal neovascularization using human retinal endothelial cells (HRECs) and PDR mice. Results: In HRECs, high glucose conditions induced oxidative stress and microvascular permeability, and K9-C-peptide suppressed those effects similarly to unconjugated human C-peptide. A single intravitreal injection of K9-C-peptide in mice resulted in the slow release of human C-peptide that maintained physiological levels of C-peptide in the intraocular space for at least 56 days without inducing retinal cytotoxicity. In PDR mice, intraocular K9-C-peptide attenuated diabetic retinal neovascularization by normalizing hyperglycemia-induced oxidative stress, vascular leakage, and inflammation and restoring blood-retinal barrier function and the balance between pro- and anti-angiogenic factors. Conclusions: K9-C-peptide provides ultra-long-lasting intraocular delivery of human C-peptide as an anti-angiogenic agent to attenuate retinal neovascularization in PDR.
Inactivating IL34 promotes regenerating muscle stem cell expansion and attenuates Duchenne muscular dystrophy in mouse models
Authors: Yang Su, Yuxin Cao, Chang Liu, Qing Xu, Na Li, Miaomiao Lan, Lei Li, Kun Wang, Zeyu Zhang, Qingyong Meng
Journal: Theranostics (2023)

Background:The balance between the differentiation and self-renewal of satellite cells (SCs) is essential for skeletal muscle homeostasis and regeneration.Our knowledge of this regulatory process is incomplete.Methods: Using global and conditional knockout mice as in vivo models and isolated satellite cells as in vitro system, we investigated the regulatory mechanisms of IL34 in the process of skeletal muscle regeneration in vivo and in vitro.Results: Myocytes and regenerating fibers are major source of IL34.Deletion of interleukin 34 (IL34) sustains expansion by sacrificing the differentiation of SCs and leads to significant muscle regeneration defects.We further found that inactivating IL34 in SCs leads to hyperactivation of NFKB1 signaling; NFKB1 translocates to the nucleus and binds to the promoter region of Igfbp5 to synergistically disturb protein kinase B (Akt) activity.Notably, augmented Igfbp5 function in SCs led to deficient differentiation and Akt activity.Furthermore, disrupting Akt activity both in vivo and in vitro mimicked the phenotype of IL34 knockout.Finally, deleting IL34 or interfering Akt in mdx mice ameliorates dystrophic muscles. Conclusion:We comprehensively characterized regenerating myofibers-expressed IL34 plays a pivotal role in controlling myonuclear domain.The results also indicate that impairing IL34 function by promoting SC maintenance can lead to improved muscular performance in mdx mice in which the stem cell pool is compromised.
Pre-metastatic niche: from revealing the molecular and cellular mechanisms to the clinical applications in breast cancer metastasis
Authors: Yuqiu Li, Miao Li, Kangtai Su, Siwen Zong, Hongyan Zhang, Lixia Xiong
Journal: Theranostics (2023)

Breast cancer (BC) is one of the most commonly diagnosed cancers and the leading cause of cancer-related deaths in women worldwide.Metastasis is a major contributor to high cancer mortality and is usually the endpoint of a series of sequential and dynamic events.One of the critical events is forming a pre-metastatic niche (PMN) that occurs before macroscopic tumor cell invasion and provides a suitable environment for tumor cells to colonize and progress into metastases.Due to the unique characteristics of PMN in cancer metastasis, developing therapies to target PMN may bring new advantages in preventing cancer metastasis at an early stage.Various biological molecules, cells, and signaling pathways are altered in BC, regulating the functions of distinctive immune cells and stromal remodeling, inducing angiogenesis, and effect metabolic reprogramming and organotropism to promote PMN formation.In this review, we elucidate the multifaceted mechanisms contributing to the development of PMN in BC, discuss the characteristics of PMN, and highlight the significance of PMN in providing potential diagnostic and therapeutic strategies for BC metastasis, which may bring promising insights and foundations for future studies.
Human iPSC-derived midbrain organoids functionally integrate into striatum circuits and restore motor function in a mouse model of Parkinson's disease
Authors: Xin Zheng, Deqiang Han, Weihua Liu, Xueyao Wang, Na Pan, Yuping Wang, Zhiguo Chen
Journal: Theranostics (2023)

Rationale: Parkinson's disease (PD) is a prevalent neurodegenerative disorder that is characterized by degeneration of dopaminergic neurons (DA) at the substantia nigra pas compacta (SNpc). Cell therapy has been proposed as a potential treatment option for PD, with the aim of replenishing the lost DA neurons and restoring motor function. Fetal ventral mesencephalon tissues (fVM) and stem cell-derived DA precursors cultured in 2-dimentional (2-D) culture conditions have shown promising therapeutic outcomes in animal models and clinical trials. Recently, human induced pluripotent stem cells (hiPSC)-derived human midbrain organoids (hMOs) cultured in 3-dimentional (3-D) culture conditions have emerged as a novel source of graft that combines the strengths of fVM tissues and 2-D DA cells. Methods: 3-D hMOs were induced from three distinct hiPSC lines. hMOs at various stages of differentiation were transplanted as tissue pieces into the striatum of naïve immunodeficient mouse brains, with the aim of identifying the most suitable stage of hMOs for cellular therapy. The hMOs at Day 15 were determined to be the most appropriate stage and were transplanted into a PD mouse model to assess cell survival, differentiation, and axonal innervation in vivo. Behavioral tests were conducted to evaluate functional restoration following hMO treatment and to compare the therapeutic effects between 2-D and 3-D cultures. Rabies virus were introduced to identify the host presynaptic input onto the transplanted cells. Results: hMOs showed a relatively homogeneous cell composition, mostly consisting of dopaminergic cells of midbrain lineage. Analysis conducted 12 weeks post-transplantation of day 15 hMOs revealed that 14.11% of the engrafted cells expressed TH+ and over 90% of these cells were co-labeled with GIRK2+, indicating the survival and maturation of A9 mDA neurons in the striatum of PD mice. Transplantation of hMOs led to a reversal of motor function and establishment of bidirectional connections with natural brain target regions, without any incidence of tumor formation or graft overgrowth. Conclusion: The findings of this study highlight the potential of hMOs as safe and efficacious donor graft sources for cell therapy to treat PD.
Perturbing plasma membrane lipid: a new paradigm for tumor nanotherapeutics
Authors: Weidong Fei, Jingjing Yan, Xiaodong Wu, Shan Yang, Xiao Zhang, Rong Wang, Yue Chen, Junjun Xu, Caihong Zheng
Journal: Theranostics (2023)

Cancer is generally considered a result of genetic mutations that cause epigenetic changes, leading to anomalous cellular behavior.Since 1970s, an increasing understanding of the plasma membrane and specifically the lipid alterations in tumor cells have provided novel insights for cancer therapy.Moreover, the advances in nanotechnology offer a potential opportunity to target the tumor plasma membrane while minimizing side effects on normal cells.To further develop membrane lipid perturbing tumor therapy, the first section of this review demonstrates the association between plasma membrane physicochemical properties and tumor signaling, metastasis, and drug resistance.The second section highlights existing nanotherapeutic strategies for membrane disruption, including lipid peroxide accumulation, cholesterol regulation, membrane structure disruption, lipid raft immobilization, and energy-mediated plasma membrane perturbation.Finally, the third section evaluates the prospects and challenges of plasma membrane lipid perturbing therapy as a therapeutic strategy for cancers.The reviewed membrane lipid perturbing tumor therapy strategies are expected to bring about necessary changes in tumor therapy in the coming decades.
Strategies for improving the 3D printability of decellularized extracellular matrix bioink
Authors: Huihui Zhang, Yilin Wang, Zijun Zheng, Xuerong Wei, Lianglong Chen, Yaobin Wu, Wenhua Huang, Lei Yang
Journal: Theranostics (2023)

3D bioprinting is a revolutionary technology capable of replicating native tissue and organ microenvironments by precisely placing cells into 3D structures using bioinks.However, acquiring the ideal bioink to manufacture biomimetic constructs is challenging.A natural extracellular matrix (ECM) is an organ-specific material that provides physical, chemical, biological, and mechanical cues that are hard to mimic using a small number of components.Organ-derived decellularized ECM (dECM) bioink is revolutionary and has optimal biomimetic properties.However, dECM is always "non-printable" owing to its poor mechanical properties.Recent studies have focused on strategies to improve the 3D printability of dECM bioink.In this review, we highlight the decellularization methods and procedures used to produce these bioinks, effective methods to improve their printability, and recent advances in tissue regeneration using dECM-based bioinks.Finally, we discuss the challenges associated with manufacturing dECM bioinks and their potential large-scale applications.
Therapeutic ultrasound combined with microbubbles improves atherosclerotic plaque stability by selectively destroying the intraplaque neovasculature: Erratum
Authors: Xinzhong Li, Shengcun Guo, Tong Xu, Xiang He, Yili Sun, Xiaoqiang Chen, Shiping Cao, Xiaoyun Si, Wangjun Liao, Yulin Liao, Yuan Han, Jianping Bin
Journal: Theranostics (2023)

[This corrects the article DOI: 10.7150/thno.39553.].
Single-cell RNA sequencing reveals a unique pericyte type associated with capillary dysfunction
Authors: Min Xia, Lyu Jiao, Xiao-Han Wang, Min Tong, Mu-Di Yao, Xiu-Miao Li, Jin Yao, Dan Li, Pei-Quan Zhao, Biao Yan
Journal: Theranostics (2023)

Background: Capillary dysfunction has been implicated in a series of life-threatening vascular diseases characterized by pericyte and endothelial cell (EC) degeneration.However, the molecular profiles that govern the heterogeneity of pericytes have not been fully elucidated.Methods: Single-cell RNA sequencing was conducted on oxygen-induced proliferative retinopathy (OIR) model.Bioinformatics analysis was conducted to identify specific pericytes involved in capillary dysfunction.qRT-PCRs and western blots were conducted to detect Col1a1 expression pattern during capillary dysfunction.Matrigel co-culture assays, PI staining, and JC-1 staining was conducted to determine the role of Col1a1 in pericyte biology.IB4 and NG2 staining was conducted to determine the role of Col1a1 in capillary dysfunction. Results:We constructed an atlas of > 76,000 single-cell transcriptomes from 4 mouse retinas, which could be annotated to 10 distinct retinal cell types.Using the sub-clustering analysis, we further characterized retinal pericytes into 3 different subpopulations.Notably, GO and KEGG pathway analysis demonstrated that pericyte sub-population 2 was identified to be vulnerable to retinal capillary dysfunction.Based on the single-cell sequencing results, Col1a1 was identified as a marker gene of pericyte sub-population 2 and a promising therapeutic target for capillary dysfunction.Col1a1 was abundantly expressed in pericytes and its expression was obviously upregulated in OIR retinas.Col1a1 silencing could retard the recruitment of pericytes toward endothelial cells and aggravated hypoxia-induced pericyte apoptosis in vitro.Col1a1 silencing could reduce the size of neovascular area and avascular area in OIR retinas and suppressed pericyte-myofibroblast transition and endothelial-mesenchymal transition.Moreover, Col1a1 expression was up-regulated in the aqueous humor of the patients with proliferative diabetic retinopathy (PDR) or retinopathy of prematurity (ROP) and up-regulated in the proliferative membranes of PDR patients.Conclusions: These findings enhance the understanding of the complexity and heterogeneity of retinal cells and have important implications for future treatment of capillary dysfunction.
Targeting HSF1 for cancer treatment: mechanisms and inhibitor development
Authors: Yeh Chin, Khanisyah E Gumilar, Xing-Guo Li, Brahmana A. Tjokroprawiro, Chien-Hsing Lu, Jianrong Lu, Ming Zhou, Robert W. Sobol, Ming Tan
Journal: Theranostics (2023)

Heat Shock Factor 1 (HSF1) is a master regulator of heat shock responsive signaling. In addition to playing critical roles in cellular heat shock response, emerging evidence suggests that HSF1 also regulates a non-heat shock responsive transcriptional network to handle metabolic, chemical, and genetic stress. The function of HSF1 in cellular transformation and cancer development has been extensively studied in recent years. Due to important roles for HSF1 for coping with various stressful cellular states, research on HSF1 has been very active. New functions and molecular mechanisms underlying these functions have been continuously discovered, providing new targets for novel cancer treatment strategies. In this article, we review the essential roles and mechanisms of HSF1 action in cancer cells, focusing more on recently discovered functions and their underlying mechanisms to reflect the new advances in cancer biology. In addition, we emphasize new advances with regard to HSF1 inhibitors for cancer drug development.
The applications of nanozymes in neurological diseases: From mechanism to design
Authors: Yuan Zhang, Lei Zhang, Man Wang, Peifeng Li
Journal: Theranostics (2023)

Nanozymes are a class of nanomaterials with enzyme-like catalytic activities.Due to their multiple catalytic activities, as well as their good stability, modifiable activity and other advantages over natural enzymes, they have a wide range of application prospects in sterilization, the treatment of inflammation, cancer, and neurological diseases, and other fields.In recent years, it has been found that various nanozymes have antioxidant activity, allowing them to simulate the endogenous antioxidant system and play an important role in cell protection.Therefore, nanozymes can be applied in the treatment of reactive oxygen species (ROS)-related neurological diseases.Another advantage of nanozymes is that they can be customized and modified in a variety of ways to increase their catalytic activity beyond that of classical enzymes.In addition, some nanozymes have unique properties, such as the ability to effectively penetrate the blood-brain barrier (BBB) or to depolymerize or otherwise eliminate misfolded proteins, making them potentially useful therapeutic tools for the treatment of neurological diseases.Here, we review the catalytic mechanisms of antioxidant-like nanozymes, as well as the latest research progress and strategies for designing therapeutic nanozymes, aiming to promote the development of more effective nanozymes for the treatment of neurological diseases in the future.